Bevacizumab increases viral distribution in human anaplastic thyroid carcinoma xenografts and enhances the effects of E1A-defective adenovirus dl922-947.
OBJECTIVE
Anaplastic thyroid carcinoma is a prime target for innovative therapy because it represents one of the most lethal human neoplasms and is refractory to conventional treatments such as chemotherapy and radiotherapy. We have evaluated a novel therapeutic approach based on the oncolytic replication-selective adenovirus dl922-947.


METHODS
The antitumor efficacies of the E1ADeltaCR2 (dl922-947) and DeltaE1B55K (dl1520) mutants were compared in human thyroid anaplastic carcinoma cells in culture and in xenografts in vivo. To enhance the effects of dl922-947, anaplastic thyroid carcinoma tumor xenografts were treated with dl922-947 in combination with bevacizumab.


RESULTS
We showed that the efficacy of dl922-947 exceeded that of dl1520 in all tested anaplastic thyroid carcinoma cells in vitro and in vivo. Furthermore, bevacizumab in combination with dl922-947 significantly reduced tumor growth compared with single treatments alone. Bevacizumab treatment significantly improved viral distribution in neoplastic tissues.


CONCLUSIONS
Our data showed that dl922-947 had a higher oncolytic activity compared with dl1520 in anaplastic thyroid carcinoma cell lines and might represent a better option for virotherapy of anaplastic thyroid carcinoma. Moreover, bevacizumab increased the oncolytic effects of dl922-947 by enhancing viral distribution in tumors. The results described herein encourage the use of the dl922-947 virus in combination with bevacizumab.
Libertini
Silvana
S
Dipartimento di Biologia e Patologia Cellulare e Molecolare, Universita di Napoli, Naples, Italy.
Iacuzzo
Irma
I
Perruolo
Giuseppe
G
Scala
Stefania
S
Ieranò
Caterina
C
Franco
Renato
R
Hallden
Gunnel
G
Portella
Giuseppe
G
D000256:Adenoviridae / Q000187:drug effects* / Q000235:genetics; D000257:Adenoviridae Infections / Q000473:pathology / Q000628:therapy / Q000821:virology; D017500:Adenovirus E1A Proteins / Q000172:deficiency; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D002277:Carcinoma / Q000473:pathology / Q000628:therapy* / Q000821:virology; D002478:Cells, Cultured; D003131:Combined Modality Therapy; D004357:Drug Synergism; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D050130:Oncolytic Virotherapy; D013964:Thyroid Neoplasms / Q000473:pathology / Q000628:therapy* / Q000821:virology; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
D017500:Adenovirus E1A Proteins; D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab